Three-dimensional breast cancer tumor models based on natural hydrogels:a review

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹ collagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

Analgesic nanomedicines for the treatment of chronic pain

Chronic pain is a major cause of suffering that often accompanies diseases and therapies,affecting approximately 20%of individuals at some point in their lives.However,current treatment modalities,such as anesthetic and antipyretic analgesics,have limitations in terms of efficacy and side effects.Nanomedical technology offers a promising avenue to overcome these challenges and introduce new therapeutic mechanisms.This article reviews the recent research on nanomedicine analgesics,integrating analyses of neuroplasticity changes in neurons and pathways related to the transition from acute to chronic pain.Furthermore,it explores potential future strategies using nanomaterials,aiming to provide a roadmap for new analgesic development and improved clinical pain management.By leveraging nanotechnology,these approaches hold the potential to revolutionize pain treatment by delivering targeted and effective relief while minimizing side effects.

Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways

Aim:Aberrant microRNA expression is a common event in cancer drug resistance,however its involvement in malignant pleural mesothelioma(MPM)drug resistance is largely unexplored.We aimed to investigate the contribution of microRNAs to the resistance to drugs commonly used in the treatment of MPM.Methods:Drug resistant MPM cell lines were generated by treatment with cisplatin,gemcitabine or vinorelbine.Expression of microRNAs was quantified using RT-qPCR.Apoptosis and drug sensitivity assays were carried out following transfection with microRNA mimics or BCL2 siRNAs combined with drugs.Results:Expression of miR-15a,miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance.Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin,gemcitabine or vinorelbine,whereas miR-34a reversed cisplatin and vinorelbine resistance only.Similarly,in parental cell lines,miR-15a or miR-16 mimics sensitised cells to all drugs,whereas miR-34a increased response to cisplatin and vinorelbine.Increased microRNA expression increased drug-induced apoptosis and caused BCL2 mRNA and protein reduction.RNAi-mediated knockdown of BCL2 partly recapitulated the increase in drug sensitivity in cisplatin and vinorelbine treated cells.Conclusion:Drug-resistant MPM cell lines exhibited reduced expression of tumour suppressor microRNAs.Increasing tumour suppressor of microRNA expression sensitised both drug resistant and parental cell lines to chemotherapeutic agents,in part through targeting of BCL2.Taken together,these data suggest that miR-15a,miR-16 and miR-34a are involved in the acquired and intrinsic drug resistance phenotype of MPM cells.